Differentiating ischemic from non-ischemic T-wave inversion

ABSTRACT

A method of discriminating between ischemic and cardiac memory effects in a heart, comprising receiving electrocardiographic (ECG) data, calculating, from the ECG data, a direction of a T-wave vector, diagnosing ischemia if the T-wave vector is between about 75 degrees and about 200 degrees, and diagnosing cardiac memory if the T-wave vector is between about zero degrees and minus 90 degrees. Also presented is a system for discriminating between ischemic and cardiac memory effects in a heart comprising means for performing an electrocardiogram, means for calculating a direction of a T-wave vector, means for diagnosing ischemia if the T-wave vector is between about 90 degrees and 180 degrees, and means for diagnosing cardiac memory if the T-wave vector is between about zero degrees and minus 90 degrees.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. application Ser. No.10/849,879, filed May 21, 2004, now U.S. Pat. No. 7,194,299 thedisclosure of which is incorporated herein in its entirety by referencethereto.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention relates to electrocardiography, and, moreparticularly, to a system and method for differentiating cardiac memoryT-wave inversion from ischemic inversion.

2. Related Art

T-wave inversion (TWI) has a wide range of etiologies, from a normalvariant to hypertrophic cardiomyopathy, pericarditis, andlife-threatening myocardial ischemia. The majority of TWI falls in acategory of “nonspecific ST-T-wave abnormalities” and accounts for 50%to 70% of abnormal tracings in general hospital populations.Interpretation of these ECGs is based primarily on correlation withavailable clinical data.

Post-pacing precordial T-wave inversions, known as cardiac memory, mimicanterior myocardial ischemia, and there are no establishedelectrocardiographic criteria that adequately distinguish between thetwo. This phenomenon is well known to cardiologists. Cardiac memory isusually exhibited when a heart is paced for some period of time, andthen the pacing is stopped. The cardiac memory effect usually depends onhow long the heart was paced, and can last anywhere from a few hours tomany weeks. Frequently, the T-wave following the pacing appearsinverted. This is commonly referred to as T-wave inversion, or TWI. Asimilar TWI effect is frequently observed in ischemic patients.Specifically, post-pacing precordial T-wave inversion mimics anteriormyocardial ischemia.

Cardiac memory is one of the benign causes of precordial TWI. ECGpatterns of cardiac memory are manifested upon resumption of a sinusrhythm after a period of abnormal ventricular activation, such asventricular pacing, transient left bundle branch block, ventriculararrhythmias, or WPW (Wolff Parkinson White syndrome). The most commoncause of cardiac memory is ventricular pacing. Because T-wave changes ofcardiac memory may persist for long periods of time after the pacing isdiscontinued, their causal relationship is often obscured. Although thebenign nature of cardiac memory TWI is well established, no reliablediagnostic mechanisms have been described to differentiatepacing-induced cardiac memory from T-wave inversions resulting fromanterior wall ischemia and infarction.

While the cardiac memory-induced T-wave inversion is a generallyharmless phenomenon that usually disappears over time, ischemia is aserious problem, normally treated by coronary angioplasty, stenting orcoronary bypass surgery. Ischemia is probably the most dangerous causeof T-wave inversion.

Because of the difficulty in distinguishing between the two causes ofTWI, as well as in distinguishing causes of TWI in patients withpacemakers, many physicians, upon seeing T-wave inversion, are compelledto perform expensive and unnecessary catheterizations, angiograms,hospital admissions, time-consuming and costly evaluations to rule outischemia, and other tests that would not be performed had the physicianknown that the T-wave inversion is due to cardiac memory, and notischemia. Most physicians, in fact, when they see an inverted T-wave,assume the worst. Similarly, much of the automated diagnostic equipment,upon detection of an inverted T-wave, gives a diagnosis of possibleischemia.

Accordingly, there is a need in the art for a simple method ofdifferentiating between benign cardiac memory-induced T-wave inversion,and ischemia-induced inversion.

SUMMARY OF THE INVENTION

The present invention relates to differentiating ischemic fromnon-ischemic T-wave inversion that substantially obviates one or more ofthe disadvantages of the related art.

Presented herein is a method of discriminating between ischemic andcardiac memory effects in a heart, comprising receivingelectrocardiographic (ECG) data, calculating, from the ECG data, adirection of a T-wave vector, diagnosing ischemia if the T-wave vectoris between about 75 degrees and about 200 degrees, and diagnosingcardiac memory if the T-wave vector is between about zero degrees andminus 90 degrees. Also presented is a system for discriminating betweenischemic and cardiac memory effects in a heart comprising means forperforming an electrocardiogram, means for calculating a direction of aT-wave vector, means for diagnosing ischemia if the T-wave vector isbetween about 90 degrees and 180 degrees, and means for diagnosingcardiac memory if the T-wave vector is between about zero degrees andminus 90 degrees.

Additional features and advantages of the invention will be set forth inthe description that follows, and in part will be apparent from thedescription, or may be learned by practice of the invention. Theadvantages of the invention will be realized and attained by thestructure particularly pointed out in the written description and claimshereof as well as the appended drawings.

It is to be understood that both the foregoing general description andthe following detailed description are exemplary and explanatory and areintended to provide further explanation of the invention as claimed.

BRIEF DESCRIPTION OF THE FIGURES

The accompanying drawings, which are included to provide a furtherunderstanding of the invention and are incorporated in and constitute apart of this specification, illustrate embodiments of the invention andtogether with the description serve to explain the principles of theinvention. In the drawings:

FIGS. 1A-1F illustrate placements of ECG leads.

FIG. 2 shows a classification of T-waves.

FIG. 3A shows a representative ECG of an ischemic patient.

FIG. 3B shows a representative ECG of a cardiac memory patient.

FIG. 4 shows T-wave amplitude in the precordial leads (V₁-V₆).

FIG. 5 shows T-wave amplitude in the limb leads.

FIG. 6 shows a circular histogram of frontal plane T axes distribution.

FIGS. 7A-7B illustrate an exemplary method of the present invention inflow chart form.

FIG. 8 shows an exemplary hardware system for differentiating TWI.

DETAILED DESCRIPTION OF THE INVENTION

Reference will now be made in detail to the preferred embodiments of thepresent invention, examples of which are illustrated in the accompanyingdrawings.

FIGS. 1A-1E illustrate the terminology used in cardiography, and FIG. 2shows exemplary electrocardiogram (ECG) traces.

FIG. 1A illustrates representative ECG waveforms taken from the twelvestandard surface leads, the six limb leads numbered I, II, III, aVR, aVLand aVF, and the six chest leads, also known as precordial leads, V₁-V₆.FIG. 1B shows positioning of the limb leads I, II and III. FIG. 1Cillustrates the connections for the limb leads I, II and III. Lead I hasa horizontal axis, going from right to left. Lead aVF has a verticalaxis, and goes top to bottom. Leads I and II are approximately 30°apart. Lead II is approximately 60° down from right to left. FIG. 1Dillustrates the connections for limb lead aVF. FIG. 1E illustrates theconnections for the limb leads aVL and aVR. FIG. 1F illustrates theplacements locations of the precordial leads V₁-V₆. Lead aVF pointsstraight down, or towards six o'clock.

Typical diagnostic equipment that is used in vector cardiography givesan angle measurement of the T-wave vector (and usually not themagnitude, since it is the vector direction that is of primaryinterest). The reader is referred to, e.g., Dale Dubin, RapidInterpretation of EKG's, 4^(th) ed., Cover Publishing Co., 1989, whichis incorporated by reference herein, for a more complete discussion oflead placements. Also, the three arteries in the heart are usuallyabbreviated as the LAD artery (left anterior descending), the circumflexartery (LCX), and the right coronary artery (RCA).

Panels A-C in FIG. 2 show examples of negative inverted T-waves (−0.8;−0.2; −0.1 mV, respectively). Panel D shows an isoelectric T-wave (0mV). Panel E shows a (normal) positive T-wave (+0.2 mV). As shown inFIG. 2, panel E, in a healthy heart, the QRS complex is followed by theS-T segment, and then followed by a positive T-wave.

Based on cardiac memory definition (post-pacing sinus rhythm T vectorapproaching direction of the paced QRS), the inventors hypothesized thatcardiac memory resulting from right ventricular pacing would have afrontal T vector direction different from that of anterior ischemic TWI,thereby enabling to discrimination between the two.

Two groups of patients were studied. The cardiac memory group consistedof thirteen patients undergoing permanent pacemaker implantation who hadsinus rhythm with 1:1 atrioventricular (AV) conduction at physiologicheart rates. None of the patients had clinical, ECG or biochemicalevidence of active ischemia. Cardiac memory was induced by one week ofAV pacing with a short atrioventricular delay. The extent of theatrioventricular delay was adjusted individually to allow ventricularactivation to proceed completely from the endocardial pacemakerelectrode positioned in the right ventricular apex. At one week, a12-lead ECG was recorded after the pacemaker was reprogrammed in AAImode. This ECG was used for analysis.

T-wave axis, polarity, and amplitude on a 12-lead ECG were comparedbetween cardiac memory and ischemic patients. The cardiac memory groupincluded eleven patients with no clinical signs of ischemia, and weresequentially paced for one week after permanent pacemaker implantation.The ischemic patient group consisted of 47 patients with precordial TWIundergoing LAD (left anterior descending) artery intervention for non-STelevation myocardial infarction. Table 1 below shows the baselinepatient data.

TABLE 1 Distribution of TWI by infarct-related artery in ischemic group.Vessel involved TWI No TWI Excluded Total LAD 28 (47%)* 31 20 79Proximal 16 (57%) 12 7 Mid, D1 12 (44%) 15 10 Distal  0‡  4 3 LCX 12(21%)  44† 17 73 RCA §  7 (11%) 56 13 76 Total 47 (26%) 131  50 228  *p< 0.05 vs. LCX and RCA groups †Including 5 patients with isolated TWI inleads I, aVL ‡p < 0.05 vs. other LAD locations § 29 patients withinferior TWI only, 1 patient with TWI in leads I, avL

Patients with preexisting ECG abnormalities were excluded, e.g.,patients with secondary TWI, such as preexisting left bundle branchblock or LVH (left ventricular hypertrophy) manifesting negative T-wavesin leads I and aVL, atrial fibrillation and ST elevation infarcts.Patients with voltage criteria for left ventricular hypertrophy werealso excluded, unless upright precordial T-waves were documented onprior tracings.

The ischemic patient group had ischemic precordial TWI due to unstableangina/non-Q wave myocardial infarction, identified retrospectivelyamong patients undergoing percutaneous coronary intervention (PCI) onone of the three major coronary arteries (LAD, LCX, RCA). If TWI waspresent on more than one ECG, the earliest ECG from index admission wasused for analysis.

Burdick Space Lab and Marquette MAC-5000 electrocardiographs were usedto record the ECGs, which were analyzed manually. T-wave amplitude wasmeasured in each lead at T-wave peak/nadir to the baseline determined byT-P segment. In case of biphasic T-waves (see, e.g., panel C in FIG. 2),the most negative deflection was taken for the peak and T-wave wasclassified as negative. T-wave was classified as isoelectric(amplitude=0) if both positive and negative components were present withan amplitude of less than 0.05 mV. QT was measured manually over threeconsecutive RR intervals in leads available on the rhythm strip(typically, lead II or lead V₅) and the results were averaged. Frontalplane QRS and T vector angles were obtained from standard automated ECGprintouts.

Clinical data was obtained from electronic medical records. Leftventricular ejection fraction, determined as a part of routine clinicalmanagement by echocardiograpy, or contrast left ventriculography, wasused for analysis if it was performed during the index admission(ischemic group) or within a year prior to the pacemaker implant(cardiac memory group).

Location of the culprit lesion within LAD system (proximal, mid) andinvolvement of the first diagonal branch (D1 branch) was determined fromangiographic reports and confirmed by visual analysis of digitalangiographic films (if report statements were unclear).

Continuous variables were expressed as mean±SEM and compared analysis ofvariance. Nominal data were compared using a Chi-square test. Angularvariables (frontal plane QRS and T-wave axes) were compared usingWatson-Williams F test. P values of less than 0.05 were consideredstatistically significant.

Baseline group characteristics are presented in Table 2 below.Male/female ratio did not differ between groups. Patients in thisischemic group were, on average, younger than in the cardiac memorygroup (65.3 vs. 72.5 years old, p<0.05). Prior ECGs were available in13/13 cardiac memory and 19/47 ischemic patients. There was nostatistically significant differences in the prevalence of baseline ECGabnormalities between ischemic and cardiac memory groups.

TABLE 2 Baseline Clinical Data Group ischemia Cardiac memory N 47 13Male, n (%) 28 (60)     6 (46)    Age, yrs 65.3 ± 2.0 72.5 ± 3.0* Priorhistory of MI, n (%)  12 (25.5%) 3 (23%) History of CABG 8 (17%) 2 (15%)Prior ECG Available 19/47  13/13* Precordial TWI 4/19 0/13 Right bundlebranch block 1/19 3/13 Q waves 4/19 2/13 *p < 0.05

All patients in the study had endocardial right ventricular apex leadimplants. Other positions within the right ventricle can producedifferent pacing QRS vectors with different resulting memory T-waves.Endocardial pacemaker implants utilize the right ventricular apex,mid-septum, or outflow tract as sites for the ventricular electrode. TheQRS complex produced by pacing from any of these sites usually has aleft axis with varying degree of superior (right ventricle apex) orinferior (right ventricle outflow tract) angulation. Therefore,post-pacing TWI will always assume a left frontal axis, no matter wherein the right ventricle the pacing lead is situated. However, with rightventricle outflow tract pacing, one would not usually see deep T-waveinversions in inferior leads, which are considered typical forpost-pacing TWI.

T-wave morphology, polarity and amplitude in precordial leads weresimilar between the two patient groups. In the cardiac memory group,T-waves in both leads I and aVL were positive or isoelectric in 13/13patients vs. 0/47 in ischemia (p<0.001). If present, inferior TWI inischemic patients invariably demonstrated a TWI |T_(II)|>|T_(III)|pattern (the subscript indicates the lead in which the T-wave wasobserved), whereas cardiac memory uniformly showed a TWI pattern|T_(III)|>|T_(II)|. T-wave patterns in limb leads were consistent withleft superior frontal plane T vector in cardiac memory and rightward inischemic patients.

Sixteen patients (57%) had a proximal LAD lesion with ischemic territoryinvolving the D1 branch. Twelve patients (44%) had a mid-LAD lesion oran isolated D1 lesion. No significant differences were found in themagnitude of T-wave inversions between proximal and mid LAD lesions aswell as between patients with and without D1 territory involvement.

CK (creatine kinase) levels were available in 27/28 LAD ischemicpatients. In seven patients, CK MB (creatine kinase myocardial branch)testing was not performed, as the total CK was <100 IU/l. Ten patientshad CK MB within the normal range (<10 ng/ml), seventeen patients (61%)had CK MB elevation ranging from 13 to 366 ng/ml (median 46 ng/ml).Twenty three patients (82%) had troponin I or T results available. Ofthose, 26 patients (93% of the LAD ischemic patients) had troponinelevation (range 0.2 to >50, median 4.2 ng/ml). All but one patient hadresults of either CK MB or troponin available.

No significant difference was observed in T-wave amplitudes in any ofthe limb leads in patients with and without CK MB elevation (<10 ng/ml).Comparison of precordial T-wave amplitudes showed a trend for deeperT-waves in patients with normal CK MB, compared to those with positiveenzyme, with differences in leads V₃ and V₅ reaching statisticalsignificance (see Table 3 below).

TABLE 3 Precordial T-wave inversion amplitude in ischemic patients with(MB+, n = 17) and without (MB−, n = 10) CK MB elevation. Leads V₁ V₂ V₃V₄ V₅ V₆ T-wave MB(+) 0.08 ± 0.04 −0.18 ± 0.08 −0.17 ± 0.06  −0.25 ±0.05 −0.18 ± 0.05  −0.07 ± 0.04 amplitude MB(−) 0.04 ± 0.06 −0.24 ± 0.13−0.45 ± 0.17* −0.42 ± 0.11 −0.26 ± 0.10* −0.15 ± 0.09 mV p 0.7 0.2 0.020.07 0.03 0.07 *p < 0.05. No relationship was found between EF and thedegree of TWI in the ischemic group.

The inventors have discovered that cardiac memory and ischemia thatcause indistinguishable precordial TWI can nonetheless be differentiatedon the basis of frontal plane T vector direction. Cardiac memory resultsin frontal T vector projection were opposite to those of anteriorischemia. A combination of positive T_(aVL) and non-inverted T_(I) waspresent in all cardiac memory patients and in none of the ischemicpatients, thus discriminating cardiac memory from ischemia. The presenceof positive T-waves in leads I and aVL provides evidence againstischemic etiology of precordial TWI.

Representative examples of ECGs are depicted in FIGS. 3A-3B. FIG. 3Ashows a representative ECG of an ischemic patient, while FIG. 3B shows arepresentative ECG of a cardiac memory patient. Both cardiac memory andischemia traces demonstrate deep T-wave inversion in the precordialleads V₁-V₆ of similar magnitude and morphology. In addition toprecordial TWI, the cardiac memory patient demonstrates deep inferiorT-wave inversion. However, a biphasic T-wave is also present in lead IIin the ischemia tracing. An important difference between recordings isseen in leads I and aVL, in which ischemia shows T-wave inversions,whereas cardiac memory manifests positive T-waves.

Electrocardiographic data is summarized in Table 3 below. The heart ratewas faster in the cardiac memory group (p<0.05) due to predominantatrial pacing in this group. Both QT and QTc intervals were notstatistically different between groups.

TABLE 3 Electrocardiographic Data ischemia Cardiac Group LAD LCX RCAmemory HR, min⁻¹ 69.4 ± 2.1 74.2 ± 3.1  66.9 ± 3.6 71.7 ± 3.7  QT, ms440 ± 10 415 ± 11  438 ± 10 417 ± 10.  QTc 415 ± 14 377 ± 16  418 ± 15 371 ± 11.4 Number of precordial  4.0 ± 0.3 3.25 ± 0.5*  2.9 ± 0.3* 4.8± 0.3 leads with TWI Maximal −0.45 ± 0.06 −0.21 ± 0.10*  −0.26 ± 0.11*−0.53 ± 0.06   precordial TWI, mV QRS frontal axis, +20 ± 7  +6 ± 11  6± 46 +18 ± 12   degrees T wave frontal +128 ± 10* +146 ± 15*   −98 ± 30−70 ± 5*   axis, degrees *p < 0.05 compared to cardiac memory group

T-wave amplitudes measured at the peak/nadir of T-wave in precordialleads were indistinguishable between CM and ISC-LAD groups (see FIG. 4,discussed below, p>0.05 for all precordial leads V₁-V₆). In contrast,all the limb leads (with the exception of aVR), showed highlysignificant differences in T-wave amplitude as well as polarity betweengroups (see FIG. 5, discussed below). The most dramatic difference wasobserved in lead aVL, where all cardiac memory patients had positiveT-waves compared to only one ischemic patient (p<0.01), whose T-wave inlead I was negative. Positive T-wave in lead I was observed in 11 out of13 cardiac memory patients, in the remaining two, the T-wave wasisoelectric, and none had negative T-waves No ischemic patients had thecombination of positive T_(aVL) and non-inverted (positive orisoelectric) T_(I). This is in contrast to all observed cardiac memorypatients.

The inventors hypothesize that, when a patient is implanted with apacemaker, one of the leads goes into the right ventricle. Pacing theheart from this lead produces negative QRS complexes in all theprecordial leads V₁-V₆. This is the reason why the T-waves are invertedwhen the pacing is stopped. By the same token, cardiac memory producespositive T-waves in leads I and aVL. Ischemia gives the same result inthe precordial leads (V₁-V₆), while it gives the opposite result inleads I and aVL. This is also due to the fact that ischemia typicallyaffects the left ventricle, and not the right ventricle. Ischemiatherefore gives negative T-waves in leads I and aVL. In other words, ina patient with cardiac memory-induced T-wave inversion, the ECG on leadsI and aVL looks normal.

FIGS. 4 and 5 illustrate the data distribution for two patientpopulations, the LAD ischemic patients and the cardiac memory patients.The open triangle symbols represent the cardiac memory patients, and theclosed (dark) triangle symbols represent the ischemic patients. FIG. 4shows T-wave amplitude in the precordial leads V₁-V₆. No significantdifference in amplitude is observed between groups. The T-wavenegativity is particularly pronounced for leads V₂-V₆, with both groupsexhibiting T-wave negativity.

FIG. 5 shows T-wave amplitude in the limb leads. Again, closed symbolsare LAD ischemic patients, open symbols are cardiac memory patients. Thedifference in amplitude between groups is statistically significant(p<0.05 for all leads except aVR). As may be seen in FIG. 5, leads I andaVL exhibit the greatest contrast in the T-waves between the two groups.With regard to both leads I and aVL, the T-waves for the cardiac memorygroup are either flat or positive, while the T-waves for the ischemicgroup are typically negative, and generally less than +0.05 millivolts.Additionally, ECG from lead III may also be used to discriminate,although not to the same extent, but lead III T waves are particularlyuseful for discriminating RCA ischemia TWI from cardiac memory.

As shown in the tables and FIGS. 4-5, all cardiac memory patients hadinverted T-waves in leads III with T_(III) deeper than V₁-V₆.

The reason for the observed differences in limb lead T-wave amplitudesbetween groups is best appreciated via vectorcardiography. While thefrontal plane QRS axis in both groups was almost identical (see Table 3above), T-wave axes differed dramatically (see also FIG. 6), with themean angle difference between groups approaching 180 degrees (+128 vs.about 71 degrees, for ischemic and cardiac memory groups, respectively,p<0.01).

FIG. 6 is a polar histogram representing the information summarized inFIGS. 4 and 5. FIG. 6 shows a polar histogram of frontal plane T axesdistribution. Filled bars are LAD ischemic patients, hatched bars areLCX ischemic patients, and open bars are cardiac memory patients. Eachcircular dashed line represents two patients. The histogram shows that atypical cardiac memory patient will show T-wave vectors generally in theapproximately −90° direction. Ischemic patients, on the other hand, willshow T-wave vectors generally between about +90° (probably from about aslow as +75°) and about +180° (probably up to about +200°). Thedifference in T vector direction between groups is statisticallysignificant (p<0.01).

In the limb leads, the same principle was observed. In the majority ofLAD and LCX patients, T waves were negative in leads I and aVL. ThreeLAD/LCX patients had positive T waves in lead I, one patient—in lead aVLand none in both leads. In vector terms, this translated intoleft-to-right direction of the T axis (see Table 4 below and FIG. 6).Limb lead TWI pattern in RCA group was variable, depending on therelative involvement of lateral and inferior leads. Four patients withpredominantly lateral precordial TWI (maximal precordial TWI amplitude >maximal inferior lead TWI amplitude) demonstrated TWI in leads I and/oraVL and left-to-right T vector axis similar to LAD and LCX groups. Threepatients with predominantly inferior lead TWI (maximal amplitudeprecordial TWI<TWI_(III)) had positive T waves in leads I and aVL.

T vector in cardiac memory group followed the direction of the paced QRScomplex. RVA pacing produced QRS that was predominantly negative inprecordial leads, negative in inferior leads and invariably positive inleads I and aVL. As a result, diffuse TWI in the precordial and inferiorleads and positive T waves in leads I and aVL were characteristic forcardiac memory. This translated into left superior T vector axisopposite in direction to that of LAD, LCX and part of RCA groups. Withthe exception of the patient with post-implant pericarditis, all cardiacmemory patients demonstrated maximal precordial TWI>TWI_(III).

Cardiac memory vs. LAD/LCX: The most dramatic difference between groupswas observed in lead aVL, where all cardiac memory patients had positiveT waves compared to only one ischemia patient, whose T wave in lead Iwas negative. Positive T wave in lead I was observed in 11/13 cardiacmemory patients; in the remaining two (both of whom had prior inferiorwall MI) T-waves were isoelectric, and none had negative T waves. Thecombination of positive T wave in lead aVL and positive/isoelectric T inlead I (criterion I+aVL) was seen in all cardiac memory patients andnone of LAD/LCX patients (see Table 4 below).

Cardiac memory vs. RCA: Four out of 7 RCA patients conformed to thepattern of LAD/LCX TWI and criterion I+aVL discriminated them fromcardiac memory. The remaining 3 RCA patients with positive T_(I) andT_(aVL) had maximal precordial |TWI|<|TWI_(III)| in contrast to all butone cardiac memory patients.

TABLE 4 Lead distribution of TWI in ischemic and cardiac memory groups,n (%). Group ischemia CM Lead LAD (n = 28) LCX (n = 12) RCA (n = 7) (n =13) V1  8 (29)  1 (8) 0  5 (39) V2 21 (75)  5 (42) 0*  8 (62) V3 22 (79) 5 (42) 1 (14)* 12 (92) V4 24 (86)  7 (58) 6 (86) 12 (82) V5 21 (75) 10(83) 6 (86) 13 (100) V6 16 (57)* 11 (92) 7 (100) 13 (100) I 20 (71)* 11(91)* 4 (57)*  0 II  8 (29)*  5 (42)* 6 (86) 13 (100) III  3 (11)*  2(17)* 4 (57)* 13 (100) aVR 10 (36)*  0 1 (14)  1 (8) aVL 23 (82)* 11(92)* 2 (29)  0 aVF  6 (21)*  4 (33)* 5 (71) 13 (100) (I + aVL)**  0* 0* 3 (43)* 13 (100) (I + aVL) and maximal 0* 12 (92) precordial TWI >TWI III *p < 0.05 with cardiac memory group **(I + aVL) - positive Twave in lead aVL, positive or isoelectric T wave in lead I.

Based on the obtained results, it is generally sufficient to look atleads I and aVL for LAD and LCX ischemia, and to consider the mostnegative component of the T-wave. If lead I shows a positive T-wave, andlead aVL shows positive or flat T-wave, while the precordial leads V₁-V₆show inverted T-waves, then the patient most likely has cardiacmemory-induced T-wave inversion. (“Positive” here is selected, forexample, to be represented as approximately 0.05 millivolts or greater.The signal is generally calibrated to 10 millimeters per millivolt onthe ECG printout.)

One embodiment of the invention may be implemented using a standarddiagnostic ECG, such as available from Burdick Space Lab or Marquette,modified to differentiate the two types of TWI according to theprinciples described above. Alternatively, although the discussion aboveis primarily in terms of using an external ECG (e.g., a standard 12-leadECG), the invention is also applicable to implantable devices. Forexample, implantable cardiac defibrillators (ICDs) usually have threeimplanted electrodes: a pacing electrodes in the right ventricle, a coil(defibrillator) electrodes in the superior vena cava, and the ICD “can”itself (usually located in the pectoral area under the skin). Usingthese electrodes (and, optionally, using additional electrodes as well,if available), the implantable device can “reconstruct” the direction ofthe T-wave vector, and, based on the direction of the T-wave vector, asdiscussed above, discriminate between cardiac memory TWI and ischemicTWI. Alternatively, the implantable device can perform mathematicaloperations on the data from the leads that generally correspond todiscriminating between the two types of TWI in the manner discussedabove, without directly calculating the T-wave vector direction.

Another exemplary hardware system for differentiating TWI is shown inFIG. 8. Referring to FIG. 8, an ECG processing system 804 is described.ECG processing system 804 includes a programmed microcomputer 8040equipped with an analog-to-digital (A/D) conversion board 8050. Thesteps of the method are performed using a software program written in,e.g., C programming language. The program follows the steps set forthabove. It is believed that any skilled programmer would have nodifficulty writing the code necessary to perform the steps of thisinvention.

Microcomputer or computer platform 8040 includes a hardware unit 8041which includes a central processing unit (CPU) 8042, a random accessmemory (RAM) 8043, and an input/output interface 8044. RAM 8043 is alsocalled a main memory. Computer platform 8040 also typically includes anoperating system 8045. In addition, a data storage device 8046 may beincluded. Storage device 8046 may include an optical disk or a magnetictape drive or disk.

Various peripheral components may be connected to computer platform8040, such as a terminal 8047, a keyboard 8048, and a printer 8049.Analog-to-digital (A/D) converter 8050 is used to sample an ECG signal.A/D converter 8050 may also provide amplification of the ECG signalprior to sampling.

FIGS. 7A-7B illustrate an exemplary method of the present invention inflow chart form. As shown in FIGS. 7A-7B, step 702 includes sensing anelectrocardiogram from a patient. Alternatively, pre-recorded data maybe analyzed. Step 704 includes identifying inverted T-waves in at leastsome of precordial leads. Step 706 includes identifying T-waves in leadsI and aVL. Steps 708-710 include diagnosing anterior ischemia if leads Iand aVL show inverted T-waves. Step 712 includes diagnosing possiblecardiac memory if the leads I and aVL show non-inverted T-waves.Optional step 714 includes identifying T-waves in lead III. Steps 715and 720 include confirming ischemia diagnosis if the lead III does notshow inverted T-waves. Optional steps 722-724 include confirmingischemic diagnosis if the lead III shows deeper inverted T-waves thanmaximum amplitude of precordial TWI. Step 725 includes confirmingcardiac memory otherwise.

It is important to note that T-wave positivity in leads I and aVL is anactive part of cardiac memory development, as an increase in T-waveamplitude is observed in the leads with a positive paced QRS complex(e.g., leads I and aVL).

The pattern of T-wave inversion in the inferior leads, if present, canalso be useful in determining the etiology of TWI. Combined ECG changesin anterior and inferior leads can be present with wrap-around LADischemia. However, in that case, the T-wave vector maintains a rightwarddirection, causing more T-wave negativity in lead II compared to leadIII, which is the opposite of the cardiac memory pattern.

As demonstrated previously in animal studies, the early stages ofcardiac memory development can be accompanied by T vector rotation inthe frontal plane before T-wave assumes the direction of pacing QRScomplex. Drugs, such as calcium channel blockers and quinidine, affectdevelopment of cardiac memory and T vector shape. At the present time,the clinical relevance of these observations remains unclear.

In the above study, the site of the culprit lesion varied between theproximal and mid-LAD (below D1) and D1 alone. Intuitively, one wouldexpect that a more lateral LV (left ventricle) spread of ischemia wouldresult in a more rightward shift of the T-wave axis. Alternatively, witha distal LAD lesion perfusing only the apical-septal left ventricle, therightward axis shift might be absent. The inventors did not observedifferences in T-wave patterns between proximal and mid-LAD lesions, norbetween lesions involving and not involving the D1 region. Therefore,there is no data to suggest that the location of LAD lesion by itselfinfluences the degree of T-wave negativity in leads I and aVL. However,no patient in the ischemic group had distal LAD lesions, and the totalnumber of patients in the study is insufficient to account for allpossible variations of coronary anatomy.

Degree of ischemia is another potential factor contributing to themagnitude of T-wave changes. The majority of ischemic patients in thestudy had positive markers for myocardial injury, signifying severeischemia. Conceivably, a lesser degree of ischemia could produce smallerT-wave changes. Counter-intuitively, when ischemic patients were dividedinto MB+ (myocardial branch (+)) and MB− (myocardial branch (−))categories, no difference between the two groups was found in T-waveamplitude in the limb leads. Moreover, marker-negative patients haddeeper precordial TWI than positive ones (see Table 4 above). Thisfinding is in accord with observations in patients having myocardialinfarction who demonstrate an inverse relationship between TWImagnitude, enzymatic size of MI (myocardial infarction) and functionalrecovery, suggesting that T-wave inversions indicate the presence of aviable stunned myocardium. Therefore, it seems unlikely that milderischemia would alter the T-wave changes in ischemic patients.

Preliminary observations suggest that cardiac memory does not change theabnormal T vector associated with these conditions Cardiac memorydevelopment might be altered in patients with prior inferior myocardialinfarction, presumably due to a lack of a viable myocardium adjacent tothe pacing site.

It is also possible that the frontal plane T vector direction can behelpful in distinguishing between ischemic and non-ischemic (but otherthan cardiac memory) precordial TWI. Several studies using precordialECG mapping showed that an I mapping pattern (inverted T-waves in theleft upper quadrant with positive T-waves in the lower right quadrant)is highly predictive of ischemic TWI. Non-ischemic TWI werecharacterized by an N pattern (TWI in lower right quadrant and positiveT-waves in left upper quadrant). These unipolar map patterns wouldlikely correspond to positive (type N) and negative (type I) T-waves inbipolar leads I, aVL, as demonstrated in previously published ECGs.

Note that the present method may not help to separate repolarizationchanges associated with LVH, the most frequent confounder of ischemicchanges, as they have similar frontal T-wave axis. Anterior wallischemia is generally regarded as the most dangerous form of ischemia.Anterior wall ischemia is generally associated with LAD (left anteriordescending) artery stenosis.

It should be noted that different locations of ischemia can result indifferent patterns of T-wave inversion. The present invention isparticularly applicable to LAD ischemia, although it is also applicable,to other forms of ischemia. Of the three arteries in the heart—the LADartery, the circumflex artery (LCX), and the right coronary artery(RCA)—in the case of LCX ischemia, sometimes there are negative T-wavesin the precordial leads, and other times, not. Thus, it should beremembered that, compared to LAD ischemia, the frequency of TWI is lessin the case of LCX ischemia. In approximately 40% of the cases, LCXischemia is accompanied by T-wave inversion in the precordial leads.

In conclusion, the invention includes the advantage of differentiatingprecordial ischemic TWI from post-pacing TWI, based on the oppositedirections of the frontal plane T-wave vectors. The inventorsdemonstrated that ischemic TWI is characterized by a rightward frontalplane T-wave axis, whereas in cardiac memory patients, the direction ofthe T vector points leftward. Bearing in mind these vector concepts, asimple discriminating rule has been devised, using standard 12-lead ECGcriteria, which is easily applicable in everyday clinical practice. Allcardiac memory patients and only one ischemic patient had positiveT-wave in lead aVL. However, the single ischemic patient with positiveT-wave in lead aVL showed a negative T-wave in lead I, a pattern notobserved in cardiac memory patients. Therefore, the combination of: 1)positive T-wave in lead aVL and 2) non-inverted (positive orisoelectric) T-wave in lead I completely discriminated cardiac memorypatients from ischemic patients. Using the most negative point in theT-wave was usually a better discriminator than using the frontal T-waveaxis, which had minimal overlap between groups. This occurs becausecalculation of T-wave axis is based on the total T-wave area (negativeand positive components) in a given lead, which in the case of biphasicT-waves dilutes the effect of terminal T-wave negativity.

By applying vectorcardiographic principles to interpretation of astandard 12-lead ECG, a simple algorithm was developed to discriminatebetween ischemic and post-pacing precordial TWI. Use of suchvectorcardiographic information can significantly improve differentialdiagnosis of TWI.

It should also be appreciated that various modifications, adaptations,and alternative embodiments thereof may be made within the scope andspirit of the present invention. The invention is further defined by thefollowing claims.

1. A method of discriminating between ischemic and cardiac memoryeffects in a heart, wherein the method is performed in an ECG processingsystem, comprising: receiving electrocardiographic data; a programmedmicrocomputer of the ECG processing system calculating, from the ECGdata, a direction of a T-wave vector; the ECG processing systemproviding a diagnosis of ischemia if the T-wave vector is between about75 degrees and about 200 degrees; and the ECG processing systemproviding a diagnosis of cardiac memory if the T-wave vector is betweenabout zero degrees and minus 90 degrees.
 2. The method of claim 1,further comprising: the ECG processing system providing a confirmationof ischemic diagnosis if leads I and aVL show inverted T-waves; and theECG processing system providing a confirmation of cardiac memorydiagnosis if leads I and aVL show non-inverted T-waves.
 3. The method ofclaim 1, further comprising: the ECG processing system providing aconfirmation of ischemic diagnosis if lead III shows deeper T-waves thanmaximal T wave inversion in the at least one precordial lead; and theECG processing system providing a confirmation of cardiac memorydiagnosis otherwise.
 4. The method of claim 1, wherein the ECGprocessing system provides a diagnosis of ischemia if the T-wave vectoris between about 90 degrees and about 180 degrees.
 5. A system fordiscriminating between ischemic and cardiac memory effects in a heartcomprising: means for performing an electrocardiogram; means forcalculating a direction of a T-wave vector; means for diagnosingischemia if the T-wave vector is between about 90 degrees and 180degrees; and means for diagnosing cardiac memory if the T-wave vector isbetween about zero degrees and minus 90 degrees.
 6. The system of claim5, wherein the T-wave vector is between about 90 degrees and about 180degrees.
 7. A method of discriminating between ischemic and cardiacmemory effects in a heart, wherein the method is performed in animplantable cardiac device, comprising: receiving electrocardiographicdata; a processor of the implantable cardiac device calculating, fromthe ECG data, a direction of a T-wave vector; the processor of theimplantable cardiac device diagnosing ischemia if the T-wave vector isbetween about 75 degrees and about 200 degrees; and the processor of theimplantable cardiac device diagnosing cardiac memory if the T-wavevector is between about zero degrees and minus 90 degrees.
 8. The methodof claim 7, further comprising: the processor of the implantable cardiacdevice confirming the ischemic diagnosis if leads I and aVL showinverted T-waves; and the processor of the implantable cardiac deviceconfirming the cardiac memory diagnosis if leads I and aVL shownon-inverted T-waves.
 9. The method of claim 7, further comprising: theprocessor of the implantable cardiac device confirming the ischemicdiagnosis if lead III shows deeper T-waves than maximal T wave inversionin the at least one precordial lead; and the processor of theimplantable cardiac device confirming the cardiac memory diagnosisotherwise.
 10. The method of claim 7, wherein the processor of theimplantable cardiac device diagnoses ischemia if the T-wave vector isbetween about 90 degrees and about 180 degrees.
 11. A method ofdifferentiating between ischemic and cardiac memory inverted T-waves,wherein the method is performed in an ECG processing system, comprising:receiving electrocardiographic data; a programmed microcomputer of theECG processing system identifying inverted T-waves in at least oneprecordial lead; the programmed microcomputer of the ECG processingsystem identifying T-waves in at least two limb leads; the programmedmicrocomputer of the ECG processing system diagnosing ischemia if the atleast one precordial lead comprises inverted T-waves; and the programmedmicrocomputer of the ECG processing system diagnosing cardiac memory ifat least one limb lead comprises non-inverted T-waves.
 12. The method ofclaim 11, wherein, in the step of identifying T-waves in at least twolimb leads, one of the two limb leads is lead I.
 13. The method of claim12, wherein, in the step of identifying T-waves in at least two limbleads, the other of the two limb leads is lead aVL.
 14. The method ofclaim 11, further comprising: the programmed microcomputer of the ECGprocessing system identifying T-waves in lead III of the limb leads; theprogrammed microcomputer of the ECG processing system confirmingischemic diagnosis if lead III shows deeper T-waves than maximal T waveinversion in the at least one precordial lead; and the programmedmicrocomputer of the ECG processing system confirming cardiac memorydiagnosis otherwise.
 15. A method of differentiating between ischemicand cardiac memory inverted T-waves, wherein the method is performed inan ECG processing system, comprising: a programmed microcomputer of theECG processing system identifying inverted T-waves in at least oneprecordial lead; the programmed microcomputer of the ECG processingsystem identifying T-waves in limb leads I, III and aVL; the programmedmicrocomputer of the ECG processing system diagnosing ischemia if theT-waves in limb lead I are inverted and the T-waves in limb lead aVL arenon-positive; the programmed microcomputer of the ECG processing systemdiagnosing ischemia if the magnitude of inverted T-waves in limb leadIII is greater than the magnitude of inverted T-waves in the at leastone precordial lead; and the programmed microcomputer of the ECGprocessing system diagnosing cardiac memory if (a) the T-waves in limblead I are non-negative or the T-waves in limb lead aVL are non-invertedT-waves and (b) the magnitude of inverted T-waves in limb lead III isnot greater than the magnitude of inverted T-waves in the at least oneprecordial lead.
 16. A method of differentiating between ischemic andcardiac memory inverted T-waves, wherein the method is performed in anECG processing system, comprising: a programmed microcomputer of the ECGprocessing system identifying inverted T-waves in at least oneprecordial lead; the programmed microcomputer of the ECG processingsystem identifying T-waves in limb leads I and aVL; the programmedmicrocomputer of the ECG processing system diagnosing ischemia if theT-waves in limb leads I and aVL are inverted T-waves; and the programmedmicrocomputer of the ECG processing system diagnosing cardiac memory ifthe T-waves in limb leads I and aVL are non-inverted T-waves.
 17. Amethod of differentiating between ischemic and cardiac memory invertedT-waves, wherein the method is performed in an implantable cardiacdevice, comprising: receiving electrocardiographic data; a processor ofthe of the implantable cardiac device identifying inverted T-waves in atleast one precordial lead; the processor of the of the implantablecardiac device identifying T-waves in at least two limb leads; theprocessor of the of the implantable cardiac device diagnosing ischemiaif the at least one precordial lead comprises inverted T-waves; and theprocessor of the of the implantable cardiac device diagnosing cardiacmemory if at least one limb lead comprises non-inverted T-waves.
 18. Themethod of claim 17, wherein, in the step of identifying T-waves in atleast two limb leads, one of the two limb leads is lead I.
 19. Themethod of claim 18, wherein, in the step of identifying T-waves in atleast two limb leads, the other of the two limb leads is lead aVL. 20.The method of claim 17, further comprising: the processor of the of theimplantable cardiac device identifying T-waves in lead III of the limbleads; the processor of the of the implantable cardiac device confirmingischemic diagnosis if lead III shows deeper T-waves than maximal T waveinversion in the at least one precordial lead; and the processor of theof the implantable cardiac device confirming cardiac memory diagnosisotherwise.
 21. A method of differentiating between ischemic and cardiacmemory inverted T-waves, wherein the method is performed in animplantable cardiac device, comprising: a processor of the of theimplantable cardiac device identifying inverted T-waves in at least oneprecordial lead; the processor of the of the implantable cardiac deviceidentifying T-waves in limb leads I, III and aVL; the processor of theof the implantable cardiac device diagnosing ischemia if the T-waves inlimb lead I are inverted and the T-waves in limb lead aVL arenon-positive; the processor of the of the implantable cardiac devicediagnosing ischemia if the magnitude of inverted T-waves in limb leadIII is greater than the magnitude of inverted T-waves in the at leastone precordial lead; and the processor of the of the implantable cardiacdevice diagnosing cardiac memory if (a) the T-waves in limb lead I arenon-negative or the T-waves in limb lead aVL are non-inverted T-wavesand (b) the magnitude of inverted T-waves in limb lead III is notgreater than the magnitude of inverted T-waves in the at least oneprecordial lead.
 22. A method of differentiating between ischemic andcardiac memory inverted T-waves, wherein the method is performed in animplantable cardiac device, comprising: a processor of the of theimplantable cardiac device identifying inverted T-waves in at least oneprecordial lead; the processor of the of the implantable cardiac deviceidentifying T-waves in limb leads I and aVL; the processor of the of theimplantable cardiac device diagnosing ischemia if the T-waves in limbleads I and aVL are inverted T-waves; and the processor of the of theimplantable cardiac device diagnosing cardiac memory if the T-waves inlimb leads I and aVL are non-inverted T-waves.